A Bioimpedance Spectroscopy-Based Method for Diagnosis of Lower-Limb Lymphedema.

Background: This study aimed at testing whether arm-to-leg ratios of extracellular water (ECW) and ECW normalized to intracellular water (ICW), measured by bioimpedance spectroscopy (BIS), can accurately detect bilateral, lower-limb lymphedema, and whether accounting for sex, age, and body mass index (BMI) improves the diagnostic performance of cut-offs. Methods and Results: We conducted a dual-approach, case-control study consisting of cases of bilateral, lower-limb lymphedema and healthy controls who self-reported absence of lymphedema. The diagnostic performance using normative data-derived cut-offs (i.e., mean + 0.5 standard deviation [SD] to mean + 3 SD; n = 136, 66% controls) and receiver operating characteristic (ROC) curve-derived cut-offs (n = 746, 94% controls) was assessed. The impact of sex, age, and BMI was investigated by comparing stratified and nonstratified normative data-derived cut-offs, and ROC curves generated from adjusted and unadjusted logistic regression models. Arm-to-leg ratios of ECW between mean + 0.5 SD and mean + 1 SD showed fair to good sensitivity (0.73-0.84) and poor to good specificity (0.64 to 0.84). Arm-to-leg ratios of ECW/ICW failed to detect lymphedema (sensitivity <0.5). Stratification by sex, or by sex and age, yielded similar results to nonstratified cut-offs. Cut-offs derived from adjusted ROC curves showed both good sensitivity (0.83-0.89) and specificity (0.8-0.84). Conclusion: These findings represent new BIS criteria for diagnosing lower-limb lymphedema that do not rely on comparison to baseline measures or the presence of a nonaffected, contralateral limb.

Normative Interlimb Impedance Ratios: Implications for Early Diagnosis of Uni- and Bilateral, Upper and Lower Limb Lymphedema.

Background: Bioimpedance spectroscopy detects unilateral lymphedema if the ratio of extracellular fluid (ECF) between arms or between legs is outside three standard deviations (SDs) of the normative mean. Detection of bilateral lymphedema, common after bilateral breast or gynecological cancer, is complicated by the unavailability of an unaffected contralateral limb. The objectives of this work were to (1) present normative values for interarm, interleg, and arm-to-leg impedance ratios of ECF and ECF normalized to intracellular fluid (ECF/ICF); (2) evaluate the influence of sex, age, and body mass index on ratios; and (3) describe the normal change in ratios within healthy individuals over time. Methods: Data from five studies were combined to generate a normative data set (n = 808) from which mean and SD were calculated for interarm, interleg, and arm-to-leg ratios of ECF and ECF/ICF. The influence of sex, age, and body mass index was evaluated using multiple linear regression, and normative change was calculated for participants with repeated measures by subtracting their lowest ratio from their highest ratio. Results: Mean (SD) interarm, interleg, dominant arm-to-leg, and nondominant arm-to-leg ratios were 0.987 (0.067), 1.005 (0.072), 1.129 (0.160), and 1.165 (0.174) for ECF ratios; and 0.957 (0.188), 1.024 (0.183), 1.194 (0.453), and 1.117 (0.367) for ECF/ICF ratios, respectively. Arm-to-leg ratios were significantly affected by sex, age, and body mass index. Mean normative change ranged from 7.2% to 14.7% for ECF ratios and from 14.7% to 67.1% for ECF/ICF ratios. Conclusion: These findings provide the necessary platform for extending bioimpedance-based screening beyond unilateral lymphedema.